General anesthesia for a surgical operation may be defined as a reversible condition, in which the patient should be unconscious by the use of a hypnotic agent, and analgesized by the use of a morphinomimetic agent and whose muscles have to be relaxed by using curares which facilitate the surgical operation.
This general anesthesia is then obtained by gas inhalation or by intravenous injection of anesthesia agents or by association thereof.
The exclusive use of intravenous anesthesia agents is a customary practice. Evaluation of the depth of the anesthesia or the titration of anesthesia agents is accomplished by clinical or paraclinical criteria.
Presently, dosage adaptation of anesthesia agents is achieved with respect to somatic modifications (movements) or those of the autonomous nervous system (tachycardia, hypertension, sweating, pupillary modifications) which are caused by surgery or which show underdosage of a drug.
However, the clinical signs are not always specific or may be absent. The movements are no longer a reliable criterion when curares are used.
Cardiovascular modifications are not specific of anesthesia agents used and may be related to surgery (bleeding, vascular clamping . . . ) or to the patient (arterial hypertension, cardiovascular treatments . . . ).
Intravenous anesthesia with a concentration target also called TCI (Target Controlled Infusion) is a method practiced for titrating the injection of a hypnotic agent or morphinomimetic agent.
This method consists of using a pharmacokinetic model of the agent which calculates a plasma concentration and/or a «effect site» concentration, i.e. at the brain, by assuming that there exists a relationship between the calculated concentration and the effect of the drug.
But, the concentrations calculated with the models have very poor correlation with the clinical condition of the patient and their use has not shown any improvement in the management of post-operative patients as compared with a standard use (i.e. in a mass perfusion) of the same anesthetic agents.
The advantage of TCI tools is to provide the physicians with the possibility of faster dosage adaptations than evolutions expressed in mass concentrations.
The presence of an anesthesiologist therefore remains indispensable during anesthesia.
However, an anesthesiologist is not always available in emergency situations, in military conflicts or when the patient cannot be moved.
A method of measuring the depth of the anesthesia or the effect of the anesthesia agents is to measure the electrocortical activity or the electroencephalogram (EEG) of the patient.
The anesthesia agents modify the morphology of the EEG signal in a way specific to each agent. However, only experienced electroencephalographists may detect these modifications. Measurement of the EEG was especially used in anesthesia during research procedures for quantifying the effect of anesthesia agents.
The real-time interpretation of changes in the EEG in the operating theatre was facilitated by the arrival of monitors which allow real-time analysis of this EEG signal. These monitors calculate different parameters from the spectral analysis of the EEG and combine them in order to provide a signal or index of anesthetic depth.
The BIS monitor of Aspect Medical System Inc. is used for measuring the anesthetic depth by calculating an index from a bi-spectral analysis of the EEG. This index varies from 0 to 100, 0 representing an isoelectric or flat line and 100 representing a line for a patient wide awake. During anesthesia, the recommendation is to maintain this index in an interval between 45 and 60 in order to obtain satisfactory conditions for performing a surgical operation. Such a monitor allows measurement of the anesthetic depth and titration of the hypnotic agent.
Indeed, it has already been suggested to use this BIS index for administering an intravenous hypnotic agent in a closed loop while sustaining anesthesia (see, for example, document U.S. Pat. No. 7,220,240), or during induction and sustainment of general anesthesia.
In the state of the art, there exists another monitor such as for example the Entropy monitor of Datex-Ohmeda Inc. This monitor quantifies disorder, i.e. entropy, in the EEG signal, this signal for an anesthetized patient being characterized by extensive, synchronized and ordered waves with little disorder and therefore low entropy.
It is then sufficient to maintain this index in the interval 40 to 60 in order to obtain satisfactory conditions for performing the surgery. This monitor provides two pieces of information, the first being called the “State Entropy (SE)” information which measures the depth of hypnosis and the second one being called the “Response Entropy (RE)” which measures the anti-nociception deficit. This monitor has already been proposed for automated perfusion of a hypnotic agent (see document U.S. Pat. No. 6,631,291, for example).